Increased circulating Th17 cell populations in patients with pancreatic ductal adenocarcinoma.

T-helper 17 (Th17) cells are a subset of CD4+ helper T cells that produce interleukin 17 (IL-17) and play a crucial role in the pathogenesis of inflammatory and autoimmune diseases. Few studies have been conducted to determine the role of Th17 cells in the tumorigenesis and development of pancreatic ductal adenocarcinoma (PDAC); however, its role is still unclear. In this study, the percentage of circulating Th17 cells and serum levels of IL-17A and IL-23 were analyzed using flow cytometry and ELISA, respectively, in 40 PDAC patients, 30 chronic pancreatitis (CP) patients and 30 healthy controls (HC). In addition, the mRNA expression levels of IL-17A, STAT3 and RORγt in tissue samples were quantified by qRT-PCR. The results showed that the percentage of circulating Th17 cells and the concentrations of serum IL-17A and IL-23 were significantly increased in PDAC patients as compared to CP and HC (P < 0.001). In addition, the higher level of IL-17A was significantly correlated with the poor overall survival of the PDAC patients. Furthermore, the frequencies of Th17 cells and IL-17A were significantly higher in stage III+IV PDAC patients versus stage I+II. A significant increase in IL-17A, STAT3 and RORγT mRNA was observed in patients with PDAC. Taken together, these findings suggest that the increased circulating Th17 cells and serum IL-17A may be involved in the development and metastasis of PDAC, and thus represent potential targets for the treatment of PDAC.

Outcomes of Portal Pressure-Guided Therapy in Decompensated Cirrhosis With Index Variceal Bleed in Asian Cohort.

BACKGROUND AND AIMS: Hemodynamic response to pharmacotherapy improves survival in patients with cirrhosis post variceal bleeding, but long-term outcomes remain unexplored especially in this part of the world. We aimed to study the long-term impact of portal pressure reduction on liver-related outcomes after index variceal bleed. METHODS: Patients with hepatic venous pressure gradient (HVPG) more than 12 mm Hg after index variceal bleed were given non-selective beta-blockers in combination with variceal band ligation. HVPG response was assessed after 4 weeks. Patients were followed up for rebleed events, survival, additional decompensation events and safety outcomes. Rebleed and other decompensations were compared using competing risks analysis, taking death as competing event, and survival was compared using Kaplan-Meier analysis. RESULTS: Forty-eight patients (29 responders and 19 non-responders) were followed up for a median duration of 45 (24-56) months. Rebleeding rates at 1, 3 and 5 years were 10.3%, 20.7% and 20.7% in responders and 15.8%, 44.7% and 51.1% in non-responders, respectively (Gray's test, P = 0.044). Survival rates at 1, 3 and 5 years were 89.7%, 72.1% and 51.9% in responders and 89.5%, 44% and 37.7% in non-responders, respectively (log-rank test, P = 0.1). Both severity of liver disease (MELD score, multivariate sub-distributional hazards ratio: 1.166 [1.014-1.341], P = 0.030) and HVPG non-response (multivariate sub-distributional hazards ratio: 2.476 [1.87-7.030], P = 0.045) predicted rebleeding risk while survival was dependent only on severity of liver disease (MELD > 12, multivariate hazards ratio: 2.36 [1.04-5.38], P = 0.041). CONCLUSION: Baseline severity of liver disease predicted survival and rebleed in these patients. Hemodynamic response, although associated with lower rebleeding rate, had limited impact on survival.

Determinants of Outcomes in Autoimmune Hepatitis Presenting as Acute on Chronic Liver Failure Without Extrahepatic Organ Dysfunction upon Treatment With Steroids.

BACKGROUND AND AIMS: Autoimmune hepatitis presenting as acute on chronic liver failure (AIH-ACLF) is a novel entity with limited data on clinical course and management. We assessed outcomes in patients of AIH-ACLF with no extrahepatic organ dysfunction/failure when administered steroids. METHODS: In this retrospective analysis, clinical data, laboratory parameters, liver biopsy indices and prognostic scores such as model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores at baseline were computed for patients with AIH-ACLF and compared across strata of incident infections and transplant-free survival. The primary outcome was 90-day transplant-free survival. Biochemical remission was assessed, and predictors of end points were identified. RESULTS: Twenty-nine patients of AIH-ACLF were included with a median follow-up of 4 months. The 90- and 180-day transplant-free survival rates of 55.2 [95% confidence interval (CI): 39.7-76.6]% and 30.2(95% CI: 16.7-54.6)%, respectively, were attained on steroids. Three patients (10.3%) underwent liver transplant while 16 (55.2%) deaths occurred. Infections developed in 12 patients (41.3%), leading to worsening prognostic scores, new onset organ dysfunction/failure and 11 deaths. Seven of ten patients (70%) in the transplant-free survivor group attained biochemical remission on follow-up. The MELD score<24 (sensitivity: 68.4%; specificity: 80%) and CTP<11 (sensitivity: 78.9%; specificity: 90%) had best predictive value for survival, in addition to decrease in the MELD score at 2 weeks (sensitivity: 78.9%; specificity: 70%). CONCLUSION: Patients with AIH-ACLF have a morbid disease course despite treatment with steroids. Patients with no extrahepatic organ failure with good baseline prognostic scores may be administered steroids with close monitoring for change in MELD over 2 weeks.

Natural course of chronic pancreatitis and predictors of its progression.

BACKGROUND: The natural course of chronic pancreatitis(CP) and its complications has been inadequately explored. We aimed to describe the natural history and factors affecting the progression of alcoholic(ACP), idiopathic juvenile(IJCP) and idiopathic senile(ISCP) variants of CP. METHODS: This study was a retrospective analysis from a prospectively maintained database of patients with CP following up at a tertiary care centre from 1998 to 2019. Cumulative rates of pain resolution, diabetes, steatorrhea, pseudocysts and pancreatic cancer were computed using Kaplan-Meier analysis, and the factors affecting their incidence were identified on multivariable-adjusted Cox-proportional-hazards model. RESULTS: A total of 1415 patients were included, with 540(38.1%) ACP, 668(47.2%) IJCP and 207(14.6%) ISCP with a median follow-up of 3.5 years(Inter-quartile range: 1.5-7.5 years). Diabetes occurred at 11.5, 28 and 5.8 years(p < 0.001) while steatorrhea occurred at 16, 24 and 18 years(p = 0.004) after onset for ACP, IJCP and ISCP respectively. Local complications including pseudocysts occurred predominantly in ACP(p < 0.001). Ten-year risk of pancreatic cancer was 0.9%, 0.2% and 5.2% in ACP, IJCP and ISCP, respectively(p < 0.001). Pain resolution occurred more frequently in patients with older age of onset[Multivariate Hazard Ratio(HR):1.7(95%CI:1.4-2.0; p < 0.001)], non-smokers[HR:0.51(95%CI:0.34-0.78); p = 0.002] and in non-calcific CP[HR:0.81(0.66-1.0); p = 0.047]. Occurrence of steatorrhea[HR:1.3(1.03-1.7); p = 0.028] and diabetes[HR:2.7(2.2-3.4); p < 0.001] depended primarily on age at onset. Occurrence of pancreatic cancer depended on age at onset[HR:12.1(4.7-31.2); p < 0.001], smoking-history[HR:6.5(2.2-19.0); p < 0.001] and non-alcoholic etiology[HR:0.14(0.05-0.4); p < 0.001]. CONCLUSION: ACP, IJCP and ISCP represent distinct entities with different natural course. Age at onset of CP plays a major prognostic role in all manifestations, with alcohol predominantly causing local inflammatory complications.